High Throughput Screening (HTS) leverages automation, chemistry, biology and information technologies to rapidly assay the pharmacologic activity of drug-like molecules. As applied to drug discovery, it has been successful for discovering the precursors of marketed drugs as well as probes of various cellular and biochemical pathways. Scripps Florida is the home of the ultra HTS (uHTS) Implementation core of the Scripps Research Institute Molecular Screening Center (SRIMSC). Core staff are responsible for developing and implementing the SRIMSC's screening assays, managing the Molecular Libraries Small Molecule Repository (MLSMR) screening collection of >360,000 samples, screening the MLSMR library at a throughput in excess of 1 million samples per day, quality control & reporting of all screening results to the NIH's publically available database (PubChem), cheminformatics support and overall project management for the SRIMSC. The core sustains full production capabilities for the NIH by screening the entire MLSMR compound library against more than 25 unique targets per year. As of this writing core staff have completed more than 185 high throughput screening campaigns for 175 molecular targets, with more than 40 million wells tested. Staff also execute lower-throughput bioassays to support the SRIMSC's hit-to-probe medicinal chemistry efforts, participating in more than 50 probe development projects per year. Target classes screened by the core include receptors, transcription factors, transferases, hydrolases, oxidoreductases, lyases, isomerases and ligases; protein interactions (protein-protein, protein-DNA, and protein-RNA) and phenotypic bioassays. Targets have been purified for screening (e.g. enzymes or proteins) or assayed in whole-cell mammalian, bacterial, insect, yeast/fungal, and parasite systems. Screening formats include biochemical enzymatic & binding affinity assays, as well as whole-cell reporter gene, second messenger, membrane potential, ion flux, complementation, protein conformation, renaturation and toxicity assays. A variety of plate-based detection formats including kinetic (FLIPR, Alphascreen, TR-FRET, FP etc.) and high content analysis (HCA) are utilized for screening efforts. More information can be found at: http://hts.florida.scripps.edu/